Abstract
Tau protein plays a critical role in the assembly, stabilization, and modulation of microtubules, which are important for the normal function of neurons and the brain. In diseased conditions, several pathological modifications of tau protein manifest. These changes lead to tau protein aggregation and the formation of paired helical filaments (PHF) and neurofibrillary tangles (NFT), which are common hallmarks of Alzheimer’s disease and other tauopathies. The accumulation of PHFs and NFTs results in impairment of physiological functions, apoptosis, and neuronal loss, which is reflected as cognitive impairment, and in the late stages of the disease, leads to death. The causes of this pathological transformation of tau protein haven’t been fully understood yet. In both physiological and pathological conditions, tau interacts with several proteins which maintain their proper function or can participate in their pathological modifications. Interaction partners of tau protein and associated molecular pathways can either initiate and drive the tau pathology or can act neuroprotective, by reducing pathological tau proteins or inflammation. In this review, we focus on the tau as a multifunctional protein and its known interacting partners active in regulations of different processes and the roles of these proteins in Alzheimer’s disease and tauopathies.
Highlights
Proteins are essential macromolecules that play important roles in almost any cellular process
In Alzheimer’s disease and other tauopathies, tau protein undergoes pathological modifications that lead to the formation of paired helical filaments (PHF) and neurofibrillary tangles (NT) which belong to the main hallmarks of these diseases
growth factor receptor-bound protein 2 (GRB2) is involved in the activation of the mitogen-activated protein kinase (MAPK) pathway leading to abnormal tau phosphorylation [587]
Summary
Proteins are essential macromolecules that play important roles in almost any cellular process. Sci. 2021, 22, 9207 potassium channels, the depletion of tau protein had a protective effect on neurons [39] These studies suggest that tau protein may play a role in the regulation of neuronal network activity in both pathological and physiological conditions. The accumulation of insoluble tau aggregates occurs inside neurons, in extracellular space [40,41], and other brain cells such as astrocytes and oligodendrocytes [42,43] The formation of this stable material is the consequence of abnormally modified and truncated tau proteins which self-aggregate and gradually mature to paired helical filaments (PHF) and neurofibrillary tangles (NFT) which are common hallmarks of several neurodegenerative diseases [44]. Tau can modulate functions of motor proteins by competitive inhibition of interactions of dynein and kinesin with microtubules, facilitating dynein binding to microtubules, or regulation of transport-vesicle releasing from motor proteins [60,61]
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